Disordered folliculogenesis is a core characteristic of polycystic ovary syndrome (PCOS) and androgen receptors (ARs) are closely associated with hyperandrogenism and abnormalities in folliculogenesis in PCOS. However, whether the new AR binding partner phosphoglycerate kinase 1 (PGK1) in granulosa cells (GCs) plays a key role in the pathogenesis of PCOS remains unclear. We identified the new AR binding partner PGK1 by co-IP (co-immunoprecipitation) in luteinized GCs, and reconfirmed by co-IP, co-localization and GST pull down assay, and checked PGK1 expression levels with qRT-PCR and western blotting. Pharmaceuticals rescue assays in mice, and metabolism assay, AR protein stability and RNA-seq of PGK1 targets in cells proved the function in PCOS. PGK1 and AR are highly expressed in PCOS luteinized GCs and PCOS-like mouse ovarian tissues. PGK1 regulated glucose metabolism and deteriorated PCOS-like mouse metabolic disorder, and paclitaxel rescued the phenotype of PCOS-like mice and reduced ovarian PGK1 and AR protein levels. PGK1 inhibited AR ubiquitination levels and increased AR stability in an E3 ligase SKP2-dependent manner. Additionally, PGK1 promoted AR nuclear translocation, and RNA-seq data showed that critical ovulation-related genes were regulated by the PGK1-AR axis. PGK1 regulated GCs metabolism and interacted with AR to regulate the expression of key ovulation genes, and also mediated cell proliferation and apoptosis, which resulted in the etiology of PCOS. This work highlights the pathogenic mechanism and represents a novel therapeutic target for PCOS. National Key Research and Development Program of China; National Natural Science Foundation of China grant.

Few studies have explored the association between a previous caesarean section (CS) and adverse perinatal outcomes in a subsequent pregnancy, especially in women who underwent a non-indicated CS in their first delivery. We designed this study to compare the perinatal outcomes of a subsequent pregnancy in women who underwent spontaneous vaginal delivery (SVD) or CS in their first delivery. This retrospective cohort study included women who underwent singleton deliveries at the International Peace Maternity and Child Health Hospital from January 2013 to December 2016. Data on the perinatal outcomes of all the women were extracted from the medical records. Multivariate logistic regression was conducted to assessed the association between CS in the first delivery and adverse perinatal outcomes in the subsequent pregnancy. CS delivery in the subsequent pregnancy was more likely for women who underwent CS in their first birth than for women with previous SVD (97.3% versus 13.2%). CS in the first birth was also associated with a significantly increased risk of adverse outcomes in the subsequent pregnancy, especially in women who underwent a non-indicated CS. Adverse perinatal outcomes included pregnancy-induced hypertension [adjusted odds ratio (OR), 95% confidence interval (CI): 2.20, 1.59–3.05], gestational diabetes mellitus (1.82, 1.57–2.11), gestational anaemia (1.27, 1.05–1.55), placenta previa (3.18, 2.15–4.71), placenta accreta (2.75, 1.75–4.31), and polyhydramnios (2.60, 1.57–4.31) in the mother and preterm delivery (1.37, 1.06–1.78), low birth weight (3.78, 2.07–6.90), macrosomia (5.04, 3.95–6.44), and neonatal jaundice (1.72, 1.39–2.14) in the baby. CS in the first delivery markedly increases the risk of repeated CS and maternal-fetal complications in the subsequent pregnancy, especially in women with a non-indicated CS.

The increasing number of babies conceived by in vitro fertilization and embryo transfer (IVF-ET) shifts concern from pregnancy outcomes to long-time health of offspring. Maternal high estradiol (E2) is a major characteristic of IVF-ET and lasts throughout the first trimester of pregnancy. The fetal thyroid develops during this period and may thus be affected by exposure to the supra-physiological E2. The aim of this study is to investigate whether the high E2 maternal environment in the first trimester increases the risk of thyroid dysfunction in children born following IVF-ET. A cross-sectional survey design was used to carry out face-to-face interviews with consecutive children attending the hospital. A total of 949 singletons born after fresh embryo transfer (ET) (n = 357), frozen ET (n = 212), and natural conception (NC) (n = 380), aged 3 to 10 years old, were included. All children were thoroughly examined. Meanwhile, another 183 newborns, including 55 fresh ET, 48 frozen ET, and 80 NC were studied. Levels of serum T3, FT3, T4, FT4, and TSH and levels of maternal E2 at different stages of the first trimester were examined. The mean serum E2 levels of women undergoing fresh ET during the first trimester of pregnancy were significantly higher than those of the women undergoing frozen ET or following NC. The thyroid hormone profile, especially the levels of T4, FT4, and TSH, were significantly increased in 3- to 10-year-old children conceived by fresh ET compared to NC. The same tendency was confirmed in newborns. However, levels of T4 and TSH in the frozen ET group were nearer to that of the NC group. Furthermore, levels of T4 and FT4 in fresh ET were positively correlated with maternal serum levels of E2 during early pregnancy. The maternal high E2 environment in the first trimester is correlated with increased risk of thyroid dysfunction. Frozen ET could reduce risks of thyroid damage in children conceived by IVF. Further studies are needed to confirm these findings and to better determine the underlying molecular mechanisms and clinical significance. ChicCTR-OCC-14004682 (22-05-2014)

To investigate the frequency and risk factors for recurrent gestational diabetes mellitus (GDM) in Chinese primiparous women. Case control study. We investigated primiparous women who experienced GDM complications and had a subsequent pregnancy in the same hospital from January, 2012 to January, 2017. Ultimately, 78 women with recurrent GDM and 64 women with no recurrence were included. Clinical characteristics and biochemical parameters such as fasting plasma glucose (FPG), oral glucose tolerance test (OGTT) and lipid profiles were collected from medical records. We used an independent t-test and Chi-square test or Fisher’s exact test to compare each variable. Univariate and multivariate logistic analyses were used to compute each odds ratio (OR) and 95% confidence interval (CI). The frequency of recurrent GDM was 55%. We found postprandial 1-h glucose at the 75-g OGTT was positively related to GDM recurrence, whereas first-trimester FPG in first pregnancy was negatively related. The first-trimester HbA1c value was higher in the group with GDM recurrence than in the group with no recurrence, though the difference was not significant. Moreover, the group with GDM recurrence manifested significantly higher first-trimester triglyceride concentrations in subsequent pregnancies; the adjusted ORs (95% CI) were 1.43 (1.09–1.87), 0.24 (0.10–0.63), 3.59 (0.93–13.88) and 1.89 (1.13–3.16). GDM recurred in more than half of subsequent pregnancies. Women with lower first-trimester FPG and higher postprandial 1-h glucose in first pregnancy, and with higher first-trimester triglyceride in subsequent pregnancy were at increased risk for GDM recurrence.

We design this study to detect levels of Elabela (ELA) and Apelin (APLN) in women with and without gestational diabetes mellitus (GDM) in the second and third trimesters, and to identify whether there is any association between ELA, APLN, and metabolic parameters. Seventy-nine GDM and 80 control subjects in the second trimester and 87 GDM and 88 healthy subjects in the third trimester were included. In the second trimester, lower ELA levels [(14.1 versus 16.9) ng/ml, p = .025] and higher APLN levels [(1021.8 versus 923.5) pg/ml, p = .046] were observed in GDM patients compared to controls. ELA levels were positively correlated with fasting plasma glucose (FPG) (r = 0.423, p < .001) in the control group, and APLN levels were negatively correlated with triglycerides (TG) (r = −0.251, p = .025) in the control group and total cholesterol (TC) (r = −0.227, p = .044) in the GDM group. ELA appeared to be related to glucose metabolism and APLN is involved in lipid metabolism during pregnancy. The expression of ELA is significantly downregulated from the second trimester to the third trimester.

Exposure to early-life undernutrition is closely related to higher risks of adverse immunologic outcomes in adulthood. Although it has been suggested that asthma has its origins in early life, its underlying mechanisms remain largely unknown. We characterized the effects of early-life undernutrition on T lymphocytes, which play a pivotal role in immune diseases, and we investigated whether this contributes to susceptibility to asthma in adulthood. Pregnant mice were fed a protein restriction diet (PRD) to establish an early-life undernutrition model. Naive CD4+ T cells (CD4+CD62LhiCD44-) from offspring were used throughout the study. TH2 differentiation was examined by using fluorescence-activated cell sorting and ELISA under TH2-polarized conditions in vitro and through ovalbumin-induced experimental asthma in vivo. T-cell metabolism was measured with a Seahorse XF96 Analyzer. DNA methylation levels were measured by using bisulfite sequencing. PRD CD4+ T cells displayed increased activation and proliferation and were prone to differentiate into TH2 cells both in vitro and in vivo, leading to susceptibility to experimental asthma. Mechanistically, early-life undernutrition upregulated mechanistic target of rapamycin 1-dependent glycolysis and induced conserved noncoding DNA sequence 1 DNA hypomethylation in the TH2 cytokine locus of CD4+ T cells. Glycolysis blockades undermined increased TH2 skewing and alleviated experimental asthma in PRD mice. Early-life undernutrition induced mechanistic target of rapamycin 1-dependent glycolysis upregulation and TH2 cytokine locus hypomethylation in CD4+ T cells, resulting in increased T-cell activation, proliferation, and TH2 skewing and further susceptibility to experimental asthma.